The objectives of this program are to attempt to understand infection of the male reproductive tract by HIV and to define mechanisms underlying sexual transmission of the virus. Several techniques developed during the initial funding period will continue to be applied to further identify cells in the male reproductive tract that can be infected by HIV and to study mechanisms of viral integration, expression and transmission. There are three specific aims, the first of which is to further identify cells in the male reproductive tract that are actively or latently infected with HIV. Previous studies will be extended to include more cases and other regions of the reproductive tract and to detect latent HIV infection in the reproductive tract by polymerase chain reaction (PCR). Secondly, the investigator proposes to determine if HIV-infected cells in the male reproductive tract are co-infected with other sexually transmitted viruses. Immunohistology (IH) and PCR studies will be performed in parallel to those in the first specific aim to identify cells in various regions of the reproductive tract that are infected with CMV or other viruses. Samples positive for both HIV and other viruses will be studied with double-label techniques to identify co-infected cells. Next, the applicant proposes further studies on mechanisms underlying HIV infection of cells in the male reproductive tract. Viable cells from various regions of normal male reproductive tissues will be incubated with HIV, HIV immune complexes or HIV-infected cells. Interaction of virus with various cell types will be studied using a variety of different techniques. Furthermore, HIV infected lymphoid and monocytic cells will be incubated with factors found in the male reproductive tract to determine if factors in the local environment affect HIV production.